CCG repeats in cDNAs from human brain

Expansion mutations of trinucleotide repeats and other units of unstable DNA have been proposed to account for at least some of the genetic susceptibility to a number of neuropsychiatric disorders, including bipolar affective disorder, schizophrenia, autism, and panic disorder. To generate additional candidate genes for these and other disorders, cDNA libraries from human brain were probed at high stringency for clones containing CCG, CGC, GCC, CGG, GCG, and GGC repeats (referred to collectively as CCG repeats). Some 18 cDNAs containing previously unpublished or uncharacterized repeats were characterized for chromosomal locus, repeat length polymorphism, and similarity to genes of known function. The cDNAs were also compared with the 37 human genes with eight or more consecutive CCG triplets in GenBank. The repeats were mapped to a number of loci, including 1p34, 2p11.2, 2q30-32 3p21, 3p22, 4q35, 6q22, 7qter, 13p13, 17q24, 18p11, 14p13.3, 20q12, 20q13.3, and 22q12. Length polymorphism was detected in 50% of the repeats. The newly cloned cDNAs in elude a complete transcript of human neurexin-1B, a portion of BCNG-1 (a newly described brain-specific ion channel), a previously unreported polymolphic repeat located in the 5' UTR legion of the guanine nucleotide-binding protein (G-protein) beta 2 subunit, and a human version of the mouse proline-rich protein 7. This list of cDNAs should expedite the search for expansion mutations associated with diseases of the central nervous system.